15-73927771-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005576.4(LOXL1):c.988C>T(p.Pro330Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000779 in 1,283,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.8e-7 ( 0 hom. )
Consequence
LOXL1
NM_005576.4 missense
NM_005576.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 1.62
Genes affected
LOXL1 (HGNC:6665): (lysyl oxidase like 1) This gene encodes a member of the lysyl oxidase family of proteins. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyzes the first step in the formation of crosslinks in collagen and elastin. The encoded preproprotein is proteolytically processed to generate the mature enzyme. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Mutations in this gene are associated with exfoliation syndrome. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25000915).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LOXL1 | NM_005576.4 | c.988C>T | p.Pro330Ser | missense_variant | 1/7 | ENST00000261921.8 | NP_005567.2 | |
LOXL1-AS1 | NR_040069.1 | n.184+294G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LOXL1 | ENST00000261921.8 | c.988C>T | p.Pro330Ser | missense_variant | 1/7 | 1 | NM_005576.4 | ENSP00000261921 | P1 | |
LOXL1-AS1 | ENST00000685373.1 | n.198+6G>A | splice_donor_region_variant, intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 7.79e-7 AC: 1AN: 1283054Hom.: 0 Cov.: 33 AF XY: 0.00000159 AC XY: 1AN XY: 630778
GnomAD4 exome
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1
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1283054
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33
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1
AN XY:
630778
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2021 | The c.988C>T (p.P330S) alteration is located in exon 1 (coding exon 1) of the LOXL1 gene. This alteration results from a C to T substitution at nucleotide position 988, causing the proline (P) at amino acid position 330 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.0023);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at